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Shanghai is the largest industrial centre in China and has a history of about 50 years in producing and applying benzidine derived dyes. A series of epidemiological studies on the carcinogenicity of benzidine and its derived dyes have been performed since 1979. This report describes three such studies. A case-control study was carried out on 344 cases of bladder cancer, each matched for age and sex, with a person without bladder cancer. Factors studied were occupational exposure, smoking, drinking, medical histories, and family history of bladder cancer and other carcinomas. The correlation between bladder cancer and occupational exposures (relative risk (RR) 5.71) was greater than that between bladder cancer and smoking (RR 1.53). A retrospective cohort study was conducted in seven dyestuffs factories where benzidine had served as an intermediate in the manufacture of dyes before 1976. The cohort was made up of 550 men and 186 women. The men were divided into two groups according to job; 354 were assigned to a presynthesis group and 196 to a postsynthesis group. Those in the presynthesis group were thought to have been exposed to benzidine and the subjects in the postsynthesis group were exposed mainly to its derived dyes. The 15 cases of bladder cancer diagnosed were all in the presynthesis group, although an excess of bladder cancer was also seen in the whole cohort. The standardised incidence ratio (SIR) of bladder cancer was 1918 in the whole cohort and 3500 in the presynthesis group. Moreover, the SIR of bladder cancer in a subgroup working directly with the assignment, transport, and mixing of benzidine was as high as 7500. A further retrospective cohort study was made on incidence of cancer among 1420 workers who used benzidine derived dyes in 43 textile printing and dyeing factories. No excess carcinoma was found. These results suggest that, in Shanghai, the main cause of bladder cancer is occupational exposure, especially to benzidine. The risk of bladder cancer, however, existed only in the presynthesis stage of dye manufacture.

To investigate the effects of benzidine (BZ) and beta-naphthylamine (BNA) on the immune system in man, the activity of natural killer (NK) cells as well as the relative number (percentage) of Leu 11a positive cells in peripheral blood lymphocytes were measured in 63 dyestuff workers exposed to BZ and BNA (aromatic amines, AA). The cytotoxic potential per NK cell (unit NK cell activity) was approximated by dividing the NK activity per fixed numbers of unseparated mononuclear cells by the percentage of Leu 11a positive lymphocytes that mediated NK activity. Thirty one of these workers had previously been treated for bladder cancer and then cured (ex-cancer AA workers) whereas the remaining 32 had not been diagnosed as having bladder cancer (non-cancer AA workers). There was no significant difference in the gross NK activity per unseparated peripheral mononuclear cells among ex-cancer AA workers, non-cancer AA workers, and the control group (p greater than 0.05). The relative number of Leu 11a positive cells, on the other hand, was significantly higher in AA workers than in the control group (p less than 0.01). The unit NK cell activity, as a result, was significantly more reduced in both ex-cancer and non-cancer AA workers than in the control group (p less than 0.05 and p less than 0.01, respectively). Between ex-cancer and non-cancer AA workers, no significant difference was observed in terms of unit NK cell activity. These results indicated that the function of NK cells per se was impaired in AA workers whereas the number of circulating NK cells was relatively increased.

Urinary benzidine and conjugates have been used to assess the extent of occupational exposure to benzidine-based azo dyes. The aim of the present study was to investigate the presence of benzidine and its conjugates in the urine of workers exposed to benzidine-derived dyes. Urine samples were collected from 29 workers in three textile dyehouses, two tanneries, and two dyestuff quality control laboratories in West Yorkshire and Lancashire. In 200 samples, obtained over a period of 15 months and analysed by gas chromatography/mass spectrometry, no free benzidine or monoacetylbenzidine was detected. Nevertheless, after strong acid hydrolysis of urine samples taken on two separate occasions from textile dye weighers where the standard of hygiene appeared below average, trace amounts of benzidine were detected suggesting the excretion of a benzidine derived dye or a metabolite thereof.

The mortality of 2926 male workers at the tanneries in the "leather area" of Tuscany was examined from 1950 to 1983 comparing it with the national mortality. Cancer mortality was of particular concern because of the many chemicals known to be definite or suspected carcinogens used in the tanning cycle, in particular chromate pigments, benzidine based dyes, formaldehyde, and organic solvents. There was no excess of deaths for cancers of all sites but slight increases in deaths from cancer of the lung (SMR = 131, CI 95% = 88-182), bladder (SMR = 150, CI 95% = 48-349), kidney (SMR = 323, CI 95% = 86-827), pancreas (SMR = 146, CI 95% = 39-373), and leukaemias (SMR = 164, CI 95% = 53-382) occurred. Two cases of soft tissue sarcomas were observed versus 0.09 expected (SMR = 2178, CI 95% = 250-8023).